The polymorphonuclear leukocyte (PMN) is a specialized cell which is geared to the intracellular destruction of microorganisms by the concentration of toxic agents within phagocytic vacuoles. Under certain conditions, these toxic PMN constituents are secreted into the extracellular fluid where they may exert a cytotoxic effect on mammalian cells. PMN-mediated tumor cell cytotoxicity will be studied using a variety of target cells and cytotoxicity assays. Emphasis will be placed on the involvement of PMN systems with known toxic activity against microorganisms and certain mammalian cells. These include the myeloperoxidase-H2O2-halide system, granular cationic proteins and toxic oxygen derivatives (superoxide anion, hydroxyl radicals, singlet oxygen). Initially, the cytotoxicity activity of these agents as cell-free systems will be examined. Once such activity is established, the cytotoxic potential of intact PMNs will be evaluated with particular attention to the involvement of the above systems. The release of lysosomal constituents and toxic metabolic products by PMNs will be induced by exposure to phagocytosable particles, antibody-coated target cells (i.e., antibody-dependent cellular cytotoxicity) and certain humoral agents (e.g., lectins). Target cell selectivity will be examined in antibody-dependent systems, by comparisons of relative sensitivity of different target cell populations to PMN cytotoxicity systems, and by studies of the specific attraction of PMNs to target cells through the formation of chemotactic factors. The primary objective of the proposed research is to delineate the function, mechanism of action, and biological significance of the PMN and other phagocytic cells in the host response to neoplastic cells.